The applicant's earlier UK application no 0121914.6 discloses a novel drug delivery technology and device for delivering an injectate. The device is intended to deliver a pioneer projectile and a following drug, and comprises an outer housing or holder, the lowermost end of which is slidably mounted within the uppermost end. At the lowermost end is fitted a disposable component, such as, for example, a drug cassette. The drug cassette is screwed into the lowermost end of the inner housing. The drug cassette comprises a casing, having a central aperture or chamber in which is mounted an injectate comprising a pioneer projectile and a formulate. A large headed ejector pin is positioned above the injectate, and when contacted by a striker in the device is pushed into a patient.
The applicant's earlier application is based on their recognition that a pioneer projectile can be used as a means for introducing medicaments in forms other than as a free flowing, non viscous liquid.
In it, they describe a method of delivering at least one therapeutic compound, or a formulation containing the at least one therapeutic compound to a human or animal in the form of a needleless injection comprising:                i) Penetrating the skin with a pioneer projectile which is left in the human or animal; and        ii) Introducing directly, or substantially directly, behind the pioneer projectile, the at least one therapeutic compound or the formulation containing the at least one therapeutic compound, which at least one therapeutic compound or the formulation containing the at least one therapeutic compound is provided in a contained state.        
By contained state is meant either:                i) As a liquid contained by a membrane;        ii) As a liquid with a viscosity of at least 5000 centipoises (the viscosity of honey), more particularly at least 50,000 (the consistency of mayonnaise) and most preferably still at least 100,000 (the consistency of peanut butter), such that the liquid has characteristics more akin to a solid than a liquid i.e. they have a definite shape as well as volume (and are not readily free flowing);        iii) As a semi-solid (having a viscosity and rigidity intermediate that of a solid or a liquid);        iv) As a paste (having a soft malleable consistency);        v) As a gel (a liquid dispersed in a solid); which materials can all be considered to have a degree of stiffness; or        vi) As a solid (a state in which the matter retains its own shape).        
Introducing a medicament in such a contained state has advantages in that splash back and seepage can be avoided and more controlled dosages delivered when compared to a following non viscous liquid formulation. The viscous, semi solid or solid nature of the medicament ensures that the pioneer projectile is pushed to the requisite depth and is followed by the medicament rather than seeping around the sides of the projectile. The semi solid formulations, gels, pastes and solids are also generally more stable than liquid formulations and are more patient compliable.
By introducing the medicament in a form other than as a non viscous liquid behind a pioneer projectile, it is possible to tailor the characteristics of the medicament for optimum pharmacokinetic delivery rather than for penetration.
Similarly the pioneer projectile can be developed to have optimised penetrating capabilities independent of the medicament.
Preferably the pioneer projectile is independent of the at least one therapeutic compound or the formulation containing the at least one therapeutic compound.
Alternatively, the pioneer projectile is independent of, yet forms an integral part of the at least one therapeutic compound or the formulation containing the at least one therapeutic compound.
Most preferably the pioneer projectile forms a head to the at least one therapeutic compound or the formulation containing the at least one therapeutic compound.
The at least one therapeutic compound or the formulation containing the at least one therapeutic compound can take a number of forms.
In one embodiment the at least one therapeutic compound or the formulation containing the at least one therapeutic compound is a liquid contained in a water soluble, lipid soluble or otherwise biodegradable membrane.
In another embodiment the at least one therapeutic compound or the formulation containing the at least one therapeutic compound is provided in a solid form such as, for example, crystals, particles, granules, beads, rods, discs or a combination thereof.
In yet another embodiment the at least one therapeutic compound or the formulation containing the at least one therapeutic compound is provided as a viscous liquid, semi solid, gel or paste which may be further supported, if desirable, by a water soluble lipid soluble or otherwise biodegradable membrane.
In the method of their earlier described invention the skin is penetrated and the therapeutic compound administered at a low velocity. By low velocity is meant less than 100 m/s. Preferably the velocity is less than 10 m/s.
Since the injectate is pushed at a low velocity rather than fired at a high velocity it is possible to ensure that the dosage is always delivered to the correct (and same) depth under the skin. This means that the system can be used on different skin types and skin locations and the dosage will still be delivered to the same depth.
This earlier application also describes novel pioneer projectiles comprising:                i) A first “penetrating” face which in use penetrates the human or animal's skin; and        ii) Remote from the first face a second “driven” face which in the course of injection is the face upon which a driving force is exerted through the therapeutic compound or therapeutic compound containing formulation; characterised in that said pioneer projectile has an aspect ratio (width to height) of less than 1:10.        
Because the pioneer projectile were developed separately of the medication, it was possible to make them less than 10 mm in length and optimise their shape such that it functions as a leading head or tip for a following formulation, the two components forming an injectate.
Preferably the pioneer projectile is water soluble, lipid soluble or otherwise biodegradable.
Preferably the pioneer projectile has an aspect ratio of less than 1:8, preferably less than 1:6, more preferably less than 1:4, more preferably still less than 1:3, and most preferably about 1:1.5.
Preferably the pioneer projectile is less than 3 mm in width, more preferably still about 1 mm in width.
Preferably the pioneer is less than 10 mm in height, more preferably about 1.5 to 2 mm in height. By reducing the height to a minimum it is possible to maximise the amount of therapeutic compound being injected. In this regard it should be noted that if the combined pioneer projectile and following drug formulation is too long it might not be possible to deliver the drug to the optimum depth.
In one embodiment, the pioneer projectile is free of any therapeutic compound. In another embodiment it comprises at least one therapeutic compound. Thus, for example it might be beneficial to include, for example an antibiotic in the pioneer projectile or have it release a therapeutic compound at a different rate to the formulation in, for example, the case of insulin injections.
The skin penetrating face of the pioneer projectile preferably comprises a cutting element to facilitate entry. This may take the form of a sharp point or an oblique edge. Alternatively the skin penetrating face may be blunt or gently curved.
In one embodiment the face for contacting the therapeutic compound or therapeutic compound containing formulation in a contained state is flat. Alternatively it may be concave or otherwise hollowed to facilitate pushing and formulation containment.
The pioneer projectile may be made of any suitable material. Suitable materials are those hard and rigid enough to facilitate penetration at low velocities. More preferred are materials, which are also water soluble, lipid soluble or otherwise biodegradable.
Preferred materials include glassy materials e.g. the sugar glasses as noted in WO 98/41188 which materials are included herein by reference.
In some circumstances the pioneer projectile may comprise a barrier material over at least the face that contacts the therapeutic compound in a contained state or vice versa such that the respective components will not react with one another.
The earlier application also discloses novel formulations. They comprise a therapeutic compound or therapeutic compound containing formulation which is held in a contained state and adapted for introduction into a human or animal in the form of a needleless injection behind a pioneer projectile.
Preferably the formulation comprises less than 50 mg of therapeutic compound in a volume of less than 50 mm3 more preferably less than 10 mg of therapeutic compound in a volume of less than 10 mm3.
The therapeutic compound or therapeutic compound containing formulation may be provided as a liquid contained in water soluble, lipid soluble or otherwise biodegradable membrane.
In an alternative embodiment the therapeutic compound or therapeutic compound containing formulation is provided in a solid form comprising for example crystals, particles, granules, beads, rods, discs or a combination thereof which are generally likely to be more stable than traditional non-viscous liquid formulations with a viscosity similar to that of water e.g. 1 Centipoises or glucose e.g. 500 Centipoises.
In a preferred embodiment the therapeutic compound or therapeutic compound containing formulation is provided as a semi solid, gel or paste. In this form it is particularly patient compliant and the therapeutic compound is generally likely to be more stable than if it were in a traditional non-viscous liquid formulation.
Where the therapeutic compound or therapeutic compound containing formulation is a viscous liquid, it preferably has a viscosity of at least 10,000 Centipoises more preferably at least 50,000 Centipoises and more preferably still at least 100,000 Centipoises.
The formulation may comprise an end piece beyond the therapeutic compound or therapeutic compound to ensure that the entire therapeutic compound enters the patient.
The therapeutic compound or therapeutic compound containing formulation may comprise a plurality of differently formulated elements.
The therapeutic compound or therapeutic compound containing formulation may be packaged in a cap, cartridge, carousel or cassette.
The applicant's earlier UK application no 0121914.6 also extends to an injectate comprising a pioneer projectile and a therapeutic compound or therapeutic compound containing formulation.
It discloses a needleless injectate for injection comprising:                a) A pioneer projectile; and        b) A therapeutic compound or therapeutic compound containing formulation which is held in a contained state behind the pioneer projectile.        
These components are as previously described.
The pioneer projectile and therapeutic compound or therapeutic compound containing formulation may both be water soluble, lipid soluble or otherwise biodegradable to differing degrees.
The injectate may be contained/packaged in a cap, cartridge, carousel or cassette optionally together with a means, e.g. an ejector pin, for pushing the pioneer injectate out of its container.
Alternatively the pioneer projectile and the therapeutic compound or therapeutic compound containing formulation are contained/packaged in separate caps, cartridges, carousels or cassettes.
The present invention incorporates all of the disclosure from this earlier UK application no 0121914.6 by reference.
An aim of the present invention is to produce a simple, cheap drug delivery device which is adaptable and able to deliver a drug in the form of not only a needleless injectate but also other forms, such as, for example liquid formulations, and solid drug needles.
This aim is achieved by the provision of a device which is adapted to receive a packaged drug which is slidably mounted in the device such that in use the device is able to push a drug from its packaging, the packaged drug being packaged such that the drug, whatever it's form, can be pushed from its packaging by the device.
It is another and independent aim to package different drug forms for use with such a device.
This aim is achieved by the provision of a packaging adapted to be attached to the device and which comprises a channel housing the drug, and a drive pin or like element for pushing it out when actuated by the device.
There are many possible product applications for such a delivery device and they include therapeutic, prophylactic and diagnostic applications. Applications may be limited to those drugs that are administered in relatively low doses because of the dose limitations for each injection imposed by pushing. However, although each dose may be limited to less than 10 mg or a volume of less than 10 mm3 it would be possible to administer more than one dose either concurrently or sequentially, if larger doses are required.
New laws in many states in the USA are declaring that safety needles must be used for injections whenever possible. These are needles that withdraw into a sheath as the needle is withdrawn from the patient so that the needle tip is not left exposed. This is to avoid the use of a conventional needle which can result in accidental needle stick injuries. A delivery system that either does not require a needle (or that incorporates a needle that retracts) would be beneficial for the US market as well as other parts of the world that will, no doubt, follow the lead of the Americans.
Particular applications where the technology might be very well suited include:
Vaccines:—Vaccinations are one of the common reasons for people to need an injection and many people would rather risk catching a disease than have to be injected with a standard needle and syringe. Children in particular can often have a needle phobia. Therefore a system that either does not incorporate a needle (or the needle is never seen by the patient) might help compliance with vaccines. In third world countries there is a great need for delivery systems for vaccines that do not involve needles. An added advantage of the new delivery system is that using a non liquid dose therapeutic compound should assist stability of the active compounds and therefore the cold chain storage requirements for the vaccine may be avoided.
Acute Emergencies:—The device is very quick and easy to use and therefore well suited for self administration as well as administration by an untrained assistant. There are a number of drugs, such as glucagon (hypoglycaemia), migraine treatments or adrenalin (anaphylactic shock) that are required when the patient may not be in a suitable condition to undertake the injection themselves. Glucagon and some of the migraine treatments are normally supplied as a powder that have to be made up with the diluent before the injection which means that they are not suitable for administration by an untrained assistant. In addition, the patient may, or may not be in a fit state to make up the drug let alone administer it. The present device would enable these and similar drugs to be administered in solid dosage form.
Diabetes:—Millions of people worldwide have to inject insulin either daily or several times a day. Most have to use a needle and syringe although new delivery systems such as inhalers and insulin pumps are becoming more popular. The advantage of the new delivery system is that several different types of insulin can be administered in a solid dose form at one tine. This can be done by having two or more short pieces of different insulin formulations in e.g. a drug cassette. This could allow a short as well as a long acting insulin to be injected at the same time and thus reduce the requirement for multiple injections throughout the day.
Although the applications above have been highlighted, the technology is suitable for administering many drugs that are required at the dosage levels capable of being delivered by the system.